Immunologic and cell culture techniques will be used to further our understanding in three areas of ocular oncology. Retinoblastoma may occur as a sporadic or germinal mutation; 10% of germinal mutation retinoblastoma survivors develop second malignancies. Genetic mechanisms are important in the development of retinoblastoma; this eye tumor may serve as an important model for inherited malignancies. The differentiation of sporadic from hereditary (germinal mutation) retinoblastoma patients may be difficult. Preliminary data demonstrates that hereditary retinoblastoma patients' fibroblasts are more sensitive to ionizing radiation than fibroblasts from sporadic retinoblastoma patients or normal controls. We will use a number of mutagenic techniques to attempt to better delineate the nature of the defects in DNA repair mechanisms in retinoblastoma. These studies may allow us to better differentiate hereditary from sporadic retinoblastoma patients, increase our knowledge regarding DNA repair defects in retinoblastoma, and predict which patients are more likely to develop second malignancies. Patients enucleated with large choroidal melanomas have approximately 50% five year tumor-related mortality. Some investigators believe that enucleation may increase mortality secondary to increased tumor cell dissemination. If this hypothesis is true, pre-operative irradiation may decrease tumor mortality. We will test, using in vitro and in vivo cell culture techniques, whether adjunct radiation will decrease the tumor cell viability and metastatic potential of these choroidal melanoma cells. The histologic differentiation of orbital pseudotumor from lymphoma has an error rate approaching 50%. We wish to use immunologic surface marker studies to better differentiate these orbital tumors which have a marked difference in prognosis. Similar technology will also be used to study the nature of lymphocyte infiltrations in uveitis and ocular reticulum cell sarcoma. It is possible that these techniques may allow us to increase both our diagnostic accuracy and basic understanding of lymphatic infiltration of ocular structures.